Reactions of Sodium Diisopropylamide: Liquid-Phase and Solid-Liquid Phase-Transfer Catalysis by N, N, N', N″, N″-Pentamethyldiethylenetriamine

Abstract

Sodium diisopropylamide (NaDA) in N,N-dimethylethylamine (DMEA) and DMEA-hydrocarbon mixtures with added N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDTA) reacts with alkyl halides, epoxides, hydrazones, arenes, alkenes, and allyl ethers. Comparisons of PMDTA with N,N,N',N'-tetramethylethylenediamine (TMEDA) accompanied by detailed rate and computational studies reveal the importance of the trifunctionality and κ²-κ³ hemilability. Rate studies show exclusively monomer-based reactions of 2-bromooctane, cyclooctene oxide, and dimethylresorcinol. Catalysis with 10 mol % PMDTA shows up to >30-fold accelerations (k_cat > 300) with no evidence of inhibition over 10 turnovers. Solid-liquid phase-transfer catalysis (SLPTC) is explored as a means to optimize the catalysis as well as explore the merits of heterogeneous reaction conditions.

Figure 1.

Metalation of 0.10 M 9 with 0.12 M NaDA in neat DMEA at −30 °C monitored by ¹H NMR spectroscopy. PMDTA (0.010 M, 0.10 equiv) was injected (see arrow).

Figure 2.

Metalation of 0.010 M cyclooctene oxide (15) with 0.12 M NaDA in 1.0 M DMEA at 25 °C monitored by ¹H NMR spectroscopy. PMDTA (0.10 equiv, 10 mol %) was injected (arrow).

Figure 3.

Plot of initial rates versus [PMDTA] in 1.0 M DMEA in hexanes cosolvent for the elimination of cyclooctene oxide (0.067 M) in the presence of 0.10 M NaDA at 25 °C. Curves depict unweighted least-squares fits to $\mathrm{y}=a\mathrm{x}∕(1+b\mathrm{x})$. Curve a (1.0 M DMEA/toluene): $a=(3.5\pm 0.9)\mathrm{x}{10}^4$; $b=(1.9\pm 0.6)\mathrm{x}{10}^4$. Curve b (neat DMEA): $a=(2.0\pm 0.2)\mathrm{x}{10}^3$; $b=(1.7\pm 0.4)\mathrm{x}{10}^3$.

Figure 4.

Plot of initial rate versus [NaDA] in 1.0 M DMEA in hexane cosolvent for the elimination of cyclooctene oxide (0.067 M) in the presence of 2.0 M PMDTA at 25 °C. The curve depicts an unweighted least-squares fit to $\mathrm{y}=k[\text{NaDA}{]}^n:k=(4.6\pm 0.7)\mathrm{x}{10}^3$; $n=0.5\pm 0.1$.

Figure 5.

Plot of initial rates versus [DMEA] in hexanes for the elimination of cyclooctene oxide with NaDA (0.10 M) in the presence of 1.5 M PMDTA at 25 °C. The curve depicts an unweighted least-squares fit to $\mathrm{y}=k[\text{DMEA}{]}^n+k’:k=(2.8\pm 0.5)\mathrm{x}{10}^3$; $k’=(1.8\pm 0.7)\mathrm{x}{10}^3$; $n=-0.8\pm 0.2$.

Figure 6.

Computed monomer-based transition structures for the elimination of cyclooctene oxide by NaDA/PMDTA (29) and NaDA/TMEDA (30).

Figure 7.

Plot of initial rates versus [TMEDA] in 1.0 M DMEA in hexanes cosolvent for the elimination of cyclooctene oxide (0.067 M) in the presence of 0.10 M NaDA at 25 °C. Curves depict unweighted least-squares fits to $\mathrm{y}=a\mathrm{x}∕(1+b\mathrm{x})+c:a=(1.7\pm 0.9)\mathrm{x}{10}^5$; $b=(1.4\pm 0.8)\mathrm{x}{10}^5$; $c=0.53$ (set by measurement).

Figure 8.

Computed transition structures for the elimination of 1-bromooctane by NaDA/PMDTA (31) and NaDA/TMEDA (32).

Figure 9.

Metalation of 0.15 M 9 with solid NaDA (equiv of 0.16 M) suspended in hexane at −15 °C monitored by GC analysis of quenched aliquots. PMDTA (0.016 M, 0.10 equiv) was injected. (See arrow.)

Figure 10.

Plot of initial rates versus [PMDTA] in hexanes for the elimination of bromooctane 9 (0.050 M) in the presence of 0.10 M NaDA at −40 °C. The curve depicts an unweighted least-squares fit to $\mathrm{y}=a{\mathrm{x}}^n:a=(1.7\pm 0.03)\mathrm{x}{10}^2$; $n=0.65\pm 0.08$.